New CityU exfoliation technique “recovers” biomaterial’s piezoelectricity

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Piezoelectric materials are applicable in the biomedical field, and if they can be biocompatible and degradable, it will be a big step towards real applications. Recently, a research team at City University of Hong Kong (CityU) developed a simple exfoliation method to prepare ultrathin films of small intestine tissues from sheep. This biological tissue has been considered to have no piezoelectric properties at the macroscale, but the CityU research team discovered that if the material is ultathin, it can show piezoelectricity. With its natural biocompatibility, the team believes that such piezoelectric biomaterial can likely be used in various biomedical applications, such as sensors and smart chips.

The research was led by Dr Yang Zhengbao, Assistant Professor in the Department of Mechanical Engineering (MNE). Their findings were published in the academic journal Advanced Materials, under the title “van der Waals Exfoliation Processed Biopiezoelectric Submucosa Ultrathin Films”.

Potential application of piezoelectric biomaterials in the biomedical field

Piezoelectricity is electricity resulting from applying pressure. Piezoelectric biomaterials have a potential effect of piezoelectricity on biological tissues, such as facilitating tissue recovery and bone regeneration, and can also be applied in implantable sensors and actuators. However, owing to the high cost and technological limitations, most research about piezoelectricity on biological tissues remains theoretical.

The 2021 Nobel Prize in Physiology or Medicine was awarded to scientists David Julius and Ardem Patapoutian, who solved the mystery of the human sensation of touch and pain. They verified that cells sense pressure and elicit the sensation of touch through the electromechanical coupling effects of the proteins Piezo 1 and Piezo 2. In fact, the piezoelectric effect is a type of electromechanical coupling effect, which widely exists in piezoelectric biological tissues, such as bones, wool, tendons and the epidermis.

On the other hand, small intestinal submucosa (SIS), which is a layer of small intestine tissues that supports the mucosa and joins it to the muscular layer, has been widely investigated. Thanks to its biocompatibility and the lack of adverse responses in cross-species transplants, small intestinal submucosa has great potential for biomedical applications and is commonly used as a “scaffolds” for repairing tissues like tendons. But does small intestinal submucosa have a piezoelectric effect?

Zhang Zhuomin, a member of Dr Yang Zhengbao’s research team, demonstrates the raw material of small intestine submucosa from sheep. (City University of Hong Kong)

“In the 1960s, renowned Japanese scientist Eiichi Fukada observed a direct but weak piezoelectric effect in intestines at the macroscopic level,” said Dr Yang. “However, owing to the technological limitations of measurement equipment at the time, quantitative determination of the intrinsic piezoelectric effect could not be demonstrated. So the reason for its biological piezoelectricity remained a mystery.”

Key to the generation of the piezoelectric effect

Before actually applying small intestine submucosa material in medical engineering, it is necessary to verify whether it can generate a piezoelectric effect and be measured quantitatively. To tackle these two key issues, Dr Yang and his team systematically investigated the structure of small intestine submucosa from sheep and its biological piezoelectricity. Eventually, for the first time, the team measured the intrinsic piezoelectric effect of small intestine submucosa quantitatively. After several rounds of measurement, the team revealed that the key to the generation of the piezoelectric effect in small intestine submucosa lay in the hierarchical structure of its collagen fibres.

Small intestine submucosa collagen fibres observed under an atomic force microscope.  (Z. Zhang, S. Liu, et al. / DOI number: 10.1002/adma.202200864)


“We found that small intestine submucosa is naturally formed with hundreds of layers of collagen fibres, with a general thickness of tens of millimetres,” said Zhang Zhuomin, Dr Yang’s PhD student and the first author of the paper. “According to our research, it is difficult to exhibit piezoelectricity at the macroscopic level of thickness in millimetres, as its intrinsic piezoelectric effect would be cancelled out within the layers. Therefore, only weak or even no piezoelectricity is detected at the macroscopic level. We discovered that making small intestine submucosa thinner could overcome the problem of cancellation and ‘recover’ piezoelectricity. This drove us to develop the proposed van der Waals exfoliation (vdWE) method to fabricate ultrathin film from small intestine submucosa.”

Figure A shows the fabrication process of ultrathin film from small intestine submucosa. Figure B is a scanning electron microscope image showing the thickness comparison between the untreated (78.5 μm) and peeled-off small intestine submucosa (8.5 μm). Figure C shows the thickness of ultrathin film by repeated peeling (about 100nm). Figure D shows ultrathin film on a silicon substrate.   (Z. Zhang, S. Liu, et al. / DOI number: 10.1002/adma.202200864)

Piezoelectricity ‘recovers’ in ultrathin status

One of the breakthroughs achieved by the team in this research is the proposed van der Waals exfoliation technique, a simple method of fabricating biopiezoelectric ultrathin film. Inspired by the processing method of two-dimensional materials such as graphene, the team made use of the weak van der Waals force between layers to fabricate single or multi-layer ultrathin film of small intestine submucosa. The ultrathin film produced by this repeated peeling method can reach a thickness of 100nm, which is nearly 800 times thinner than that of the non-exfoliated original material.

Using prepared small intestine submucosa ultrathin film, the team performed a quantitative study probing the biological piezoelectricity and determined the origin of its biological piezoelectricity.

Small intestine submucosa exhibits an increase in the effective piezoelectric coefficient with a decrease in film thickness up to a saturated level of about 3.3 pm/V. (Z. Zhang, S. Liu, et al. / DOI number: 10.1002/adma.202200864)

“The films exhibited an increase in the effective piezoelectric coefficient with a decrease in film thickness, up to a saturated level of about 3.3 pm/V,” said Dr Yang. “Based on our vdWE technique, the piezoresponse of the ultrathin films is increased by more than 20 times compared with the non-exfoliated original films. Since the problem of cancellation of piezoelectricity is overcome in the ultrathin film, we can detect piezoelectricity, thus making the application of piezoelectric biological tissues possible.”

The research team put the small intestinal submucosa ultrathin film on a silicon substrate to further investigate its application.  (City University of Hong Kong)

The research team also designed a biosensor to verify the practical application of piezoelectricity in the small intestinal submucosa ultrathin film. The team found that its natural biocompatibility, flexibility and piezoelectricity make it a promising and ecologically friendly material for electromechanical microdevices in implantable and wearable electronics. The vdWE technique that the team proposed is facile and environmentally friendly, and also can be applied to various biological soft tissue materials with van der Waals layered structures, such as fish bladders and cow achilles tendons.

Members of Dr Yang’s research team and the first authors of the paper, Zhang Zhuomin (left) and Liu Shiyuan (right), from the MNE. They used the atomic force microscope behind them to observe piezoelectricity in small intestinal submucosa. (City University of Hong Kong)

Dr Yang is the corresponding author of the paper. The first authors are PhD students Zhang Zhuomin and Liu Shiyuan, from CityU’s MNE. Dr Chai Yu, Assistant professor in CityU’s Department of Physics, Dr Peng Zehua, Postdoc in the MNE, PhD students Pan Qiqi, Hong Ying, Shan Yao, Xu Xiaote, and master’s student Liu Bingren also participated in the research.

The research was supported by the Research Grants Council of Hong Kong and the National Natural Science Foundation of China.


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